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Percent Atheroma Volume: Optimal Variable to Report Whole-Heart T Atherosclerotic Plaque Burden with Coronary CTA, the PARADIGM Study Alexander R

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Percent Atheroma Volume: Optimal Variable to Report Whole-Heart T Atherosclerotic Plaque Burden with Coronary CTA, the PARADIGM Study Alexander R Journal of Cardiovascular Computed Tomography 14 (2020) 400–406 Contents lists available at ScienceDirect Journal of Cardiovascular Computed Tomography journal homepage: www.elsevier.com/locate/jcct Research paper Percent atheroma volume: Optimal variable to report whole-heart T atherosclerotic plaque burden with coronary CTA, the PARADIGM study Alexander R. van Rosendaela,b, Fay Y. Lina, Xiaoyue Mac, Inge J. van den Hoogena,b, Umberto Giannia,d, Omar Al Husseina, Subhi J. Al'Arefa, Jessica M. Peñaa, Daniele Andreinie, Mouaz H. Al-Mallahf, Matthew J. Budoffg, Filippo Cademartirih, Kavitha Chinnaiyani, Jung Hyun Choij, Edoardo Contee, Hugo Marquesk, Pedro de Araújo Gonçalvesk, Ilan Gottliebl, Martin Hadamitzkym, Jonathon A. Leipsicn, Erica Maffeio, Gianluca Pontonee, Gilbert L. Raffi, Sanghoon Shinp, Yong-Jin Kimq, Byoung Kwon Leer, Eun Ju Chuns, Ji Min Sungt,u, Sang-Eun Leet,u, Daniel S. Bermanv, Renu Virmaniw, Habib Samadyx, Peter H. Stoney, ∗ Jagat Narulaz, Jeroen J. Baxb, Leslee J. Shawa, James K. Mina, , Hyuk-Jae Changt a Department of Radiology, NewYork-Presbyterian Hospital and Weill Cornell Medicine, New York, NY, USA b Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands c Department of Healthcare Policy and Research, New York-Presbyterian Hospital and the Weill Cornell Medical College, New York, NY, USA d Department of Molecular Medicine, Section of Cardiology, University of Pavia, Pavia, Italy e Centro Cardiologico Monzino, IRCCS Milan, Italy f Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, TX, USA g Department of Medicine, Los Angeles Biomedical Research Institute, Torrance, CA, USA h Cardiovascular Imaging Center, SDN IRCCS, Naples, Italy i Department of Cardiology, William Beaumont Hospital, Royal Oak, MI, USA j Pusan University Hospital, Busan, South Korea k UNICA, Unit of Cardiovascular Imaging, Hospital da Luz, Lisboa, Portugal l Department of Radiology, Casa de Saude São Jose, Rio de Janeiro, Brazil m Department of Radiology and Nuclear Medicine, German Heart Center Munich, Munich, Germany n Department of Medicine and Radiology, University of British Columbia, Vancouver, BC, Canada o Department of Radiology, Area Vasta 1/ASUR Marche, Urbino, Italy p Division of Cardiology, Department of Internal Medicine, Ewha Womans University Seoul Hospital, Seoul, South Korea q Department of Internal Medicine, Seoul National University College of Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea r Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea s Seoul National University Bundang Hospital, Sungnam, South Korea t Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea u Yonsei-Cedars-Sinai Integrative Cardiovascular Imaging Research Center, Yonsei University College of Medicine, Yonsei University Health System, South Korea v Department of Imaging and Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA w Department of Pathology, CVPath Institute, Gaithersburg, MD, USA x Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA y Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA z Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, Zena and Michael A. Wiener Cardiovascular Institute, Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, New York, NY, USA ARTICLE INFO ABSTRACT Keywords: Background and aims: Different methodologies to report whole-heart atherosclerotic plaque on coronary com- Atherosclerosis puted tomography angiography (CCTA) have been utilized. We examined which of the three commonly used Imaging plaque burden definitions was least affected by differences in body surface area (BSA) and sex. Percent atheroma volume Methods: The PARADIGM study includes symptomatic patients with suspected coronary atherosclerosis who Coronary CTA underwent serial CCTA > 2 years apart. Coronary lumen, vessel, and plaque were quantified from the coronary tree on a 0.5 mm cross-sectional basis by a core-lab, and summed to per-patient. Three quantitative methods of plaque burden were employed: (1) total plaque volume (PV) in mm3, (2) percent atheroma volume (PAV) in % ∗ Corresponding author. E-mail address: [email protected] (J.K. Min). https://doi.org/10.1016/j.jcct.2020.01.012 Received 20 August 2019; Received in revised form 5 November 2019; Accepted 29 January 2020 Available online 30 January 2020 1934-5925/ © 2020 Published by Elsevier Inc. on behalf of Society of Cardiovascular Computed Tomography A.R. van Rosendael, et al. Journal of Cardiovascular Computed Tomography 14 (2020) 400–406 3 [which equaled: PV/vessel volume * 100%], and (3) normalized total atheroma volume (TAVnorm) in mm [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAVnorm were compared between patients in the top quartile of BSA vs the remaining, and between sexes. Associations between vessel volume, BSA, and the three plaque burden methodologies were assessed. Results: The study population comprised 1479 patients (age 60.7 ± 9.3 years, 58.4% male) who underwent CCTA. A total of 17,649 coronary artery segments were evaluated with a median of 12 (IQR 11–13) segments per-patient (from a 16-segment coronary tree). Patients with a large BSA (top quartile), compared with the remaining patients, had a larger PV and TAVnorm, but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAVnorm) was mediated by the coronary vessel volume. Independent from the atherosclerotic cardiovascular disease risk (ASCVD) score, vessel volume correlated with PV (P < 0.001), and TAVnorm (P = 0.003), but not with PAV (P = 0.201). The three plaque burden methods were equally affected by sex. Conclusions: PAV was less affected by patient's body surface area then PV and TAVnorm and may be the preferred method to report coronary atherosclerotic burden. 1. Introduction data from the baseline CCTA were used. Coronary computed tomography angiography (CCTA) allows for accurate evaluation of atherosclerotic plaque, and its presence, extent and severity are strongly related to future major adverse cardiovascular 2.2. CCTA imaging and analysis protocol events.1 More recently, studies have demonstrated the ability of CCTA to accurately quantify the total coronary plaque burden (whole-heart) CCTAs were acquired using ≥64 detector row CT scanners, with 2–5 and to assess changes in plaque burden on CCTA over time. image acquisition protocols in accordance with the Society of Plaque burden with intravascular ultrasound (IVUS) has tradition- Cardiovascular Computed Tomography guidelines, including the sys- ally been reported using percent atheroma volume (PAV)—defined as tematic administration of beta-blocker and nitroglycerin before acqui- the total plaque volume (PV)/vessel volume x 100%—or total atheroma sition.10 CCTA DICOM files from each participating site were trans- volume normalized to vessel length (TAVnorm)—defined as PV/vessel ferred to a Central Core Laboratory for blinded image analysis. Level III 6,7 length x mean population vessel length. Normalization is performed experienced CTA readers from the Central Core Laboratory, masked to to adjust for differences in the length of the interrogated coronary patient clinical and demographical characteristics, performed qualita- segments. Compared with IVUS, CCTA offers the ability to quantify and tive and semi-quantitative CCTA analysis using dedicated software characterize atherosclerotic plaque from all coronary artery segments (QAngioCT Research Edition v2.1.9.1; Medis Medical Imaging Systems, simultaneously, albeit at a lower spatial resolution. This allows for Leiden, the Netherlands).5 CCTA imaging analysis methodology in- whole-heart atherosclerotic plaque assessment by total PV without cluded routine measures of inter- and intra-observer variability, as has 2,3 normalization for vessel length or volume. To date, no study—either been described previously: intra-class correlation coefficient 0.992 for by CCTA or IVUS—has examined how PV, PAV or TAVnorm are influ- inter-observer, and 0.996 for intra-observer plaque volume repeat- enced by scenarios that affect vessel length and vessel volume. Previous ability.5,11 In brief, measures of coronary plaque, lumen and vessel wall histological and imaging data has shown that the size of arteries is were assessed in all coronary segments ≥2 mm in diameter, using 8,9 dependent on body surface area (BSA) and sex. standardized width/level display settings adjusted for aortic contrast The ideal method for determining atherosclerotic plaque burden attenuation. Contours were manually adjusted where needed. Coronary would be least affected – most stable – to patient demographics. PV (no plaque was defined as any tissue ≥1 mm2 within or adjacent to the normalization of plaque), PAV (normalization for vessel volume), and lumen that can be distinguished from the surrounding pericardial 1 TAVnorm (normalization for vessel length) may vary according to BSA tissue, epicardial fat or the coronary artery lumen. Measurements were and sex – which are known to affect vessel size (length and volume). In performed per-segment on a 0.5 mm cross-sectional basis according to a a large, prospective CCTA study with whole-heart quantification of modified 16-segment coronary
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